Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Diabet Med. 2011 Jun;28(6):685-91. doi: 10.1111/j.1464-5491.2011.03252.x.
Asymmetric dimethylarginine (ADMA) is an independent risk factor for cardiovascular disease and its concentrations are increased in several diseases, including diabetes. However, there is limited information on this plasma marker in young people, particularly in those with Type 1 diabetes. The aim of the present study was therefore to perform a longitudinal evaluation of plasma ADMA and of its determinants in young people with childhood-onset Type 1 diabetes.
For measurement of ADMA using mass spectrometry, 1018 longitudinal stored blood samples were available from 330 young people with Type 1 diabetes followed in the Oxford Regional Prospective Study. Additional data concerning annual assessments of HbA(1c) , height, weight, insulin dose and three early morning urine samples for measurement of the albumin/creatinine ratio were available.
ADMA levels were significantly higher in males than in females (mean ± SD: 0.477 ± 0.090 vs. 0.460 ± 0.089 μmol/l, P=0.002) and declined with chronological age (estimate ± SE: -0.0106 ± 0.0008, P<0.001). A significant inverse association was detected between ADMA and HbA(1c) (estimate ± SE:-0.0113 ± 0.001, P<0.001). ADMA levels were lower in subjects developing microalbuminuria (mean ± SD: 0.455 ± 0.093 vs. 0.476 ± 0.087 μmol/l, P=0.001) than in subjects with normoalbuminuria, but this difference disappeared after adjusting for HbA(1c) .
In this longitudinal study, ADMA concentrations decreased with age and were significantly higher in males and lower in subjects developing microalbuminuria. These associations were largely explained by a paradoxical negative association between HbA(1c) and ADMA. We suggest that chronic hyperglycaemia might down-regulate mechanisms implicated in ADMA production or stimulate its metabolism confounding short-term associations with complications risk.
不对称二甲基精氨酸（ADMA）是心血管疾病的独立危险因素，其浓度在多种疾病中升高，包括糖尿病。然而，关于这种血浆标志物在年轻人中的信息有限，特别是在 1 型糖尿病患者中。因此，本研究的目的是对儿童期发病的 1 型糖尿病患者进行 ADMA 的纵向评估及其决定因素。
使用质谱法测量 ADMA，我们可从在牛津地区前瞻性研究中随访的 330 名 1 型糖尿病年轻患者中获得 1018 个纵向储存的血样。还可获得有关每年评估 HbA1c、身高、体重、胰岛素剂量和 3 个晨尿样以测量白蛋白/肌酐比值的额外数据。
ADMA 水平在男性中显著高于女性（均值±SD：0.477±0.090 vs. 0.460±0.089 μmol/L，P=0.002），并随年龄呈下降趋势（估计值±SE：-0.0106±0.0008，P<0.001）。ADMA 与 HbA1c 呈显著负相关（估计值±SE：-0.0113±0.001，P<0.001）。与无微量白蛋白尿患者相比，发生微量白蛋白尿的患者 ADMA 水平较低（均值±SD：0.455±0.093 vs. 0.476±0.087 μmol/L，P=0.001），但在调整 HbA1c 后这种差异消失。
在这项纵向研究中，ADMA 浓度随年龄下降，在男性中显著升高，在发生微量白蛋白尿的患者中降低。这些关联主要是由于 HbA1c 和 ADMA 之间存在矛盾的负相关。我们认为，慢性高血糖可能下调 ADMA 产生所涉及的机制或刺激其代谢，从而混淆了与并发症风险的短期关联。
